In 1980, we initiated a series of neuropsychological studies of children, 10 to 19 years of age, with and without type 1 diabetes. We found that those who developed diabetes within the first 5 or 6 years of life were more likely to manifest widespread, clinically significant cognitive impairment, as compared to those with a later age at diagnosis, or to nondiabetic comparison subjects. Although the underlying pathophysiological mechanism remains controversial, we now believe that occurrence of diabetes-associated chronic hyperglycemia during a critical period of brain" development adversely affects the central nervous system, and increases its vulnerability to subsequent brain insults, particularly those associated with moderately severe hypoglycemic episodes. Whether these deficits reflect reversible developmental delays, or whether they are evidence of permanent brain damage (which may worsen over time) remains unknown, as does their effect on adult functioning. The goal of our proposed study is to re-contact those individuals first seen by us between 1980 and 1983 (Mean age = 14.5 yrs; initial number: 226) and invite them to complete a detailed neuropsychological assessment, a psychiatric diagnostic interview, and measures of quality of life and vocational adjustment. Diabetic subjects will also have a physical examination with tests to ascertain biomedical complications and review of prior hypoglycemic episodes. Our study has two broad aims: First, to test the early onset vulnerability hypothesis, predicting that adults diagnosed with diabetes before 6 years of age will show greater deterioration in cognitive functioning over time, compared to those with a later onset of diabetes, that all cognitive domains will be affected, that this will eventuate in less vocational attainment and poorer quality of life, and that this will be predicted by number of intercurrent episodes of hypoglycemia, as well as by the incidence of diabetic complications. Second, we aim to provide a comprehensive profile of diabetic patients' neuropsychiatric status in middle-adulthood, with determination of the extent to which hypoglycemic events as well as other biomedical and psychosocial factors predict those outcomes. This will be the first study of diabetic patients to delineate changes in cognitive functioning from late childhood into middle-adulthood, and the first to link functional changes to diabetes-related biomedical variables. [unreadable] [unreadable]